Nature Genetics Contents: October 2013 pp 1103 - 1261

Advertisement Super Capabilities are Now Within Your Reach. Experience the LightCycler® 96 Instrument's intuitive user interface and powerful analysis software. Innovative optics, cutting-edge thermal resolution and data reproducibility enable research breakthroughs.  Find out how to become a scientific Superhero! TABLE OF CONTENTS October 2013 Volume 45, Issue 10 Focus Editorial News and Views Research Highlights Commentaries Analysis Articles Letters Corrigenda Advertisement NOW WITH EVEN MORE Now, as a part of the Quintiles family, Expression Analysis offers more expertise, more global reach and more ways to help you succeed. Read about our genomics capabilities from discovery through clinical development. 919-405-2248 * 866-293-6094 Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement CHAIR, GENETICS & MEDICAL GENETICS The University of Wisconsin invites applications and nominations for the position of Chair of the combined Departments of Genetics and Medical Genetics in the College of Agricultural and Life Sciences (CALS) and the School of Medicine and Public Health (SMPH) respectively, at the University of Wisconsin.  Click here for a complete description and application requirements.   Advertisement Get the most from your NGS data with Sequenom's MassARRAY® system Validate from tens to thousands of samples across tens to hundreds of SNPs Design your own assays against any SNP of interest Run a variety of applications including genotyping, DNA methylation and somatic mutation analysis   Focus Top Focus on TCGA Pan-Cancer Analysis Focus issue: October 2013 Volume 45, No 10 Contents Foreword Editorial Analysis Commentaries Editorial Top Targeting molecular tumor types   p1103 doi:10.1038/ng.2780 In this issue, the Focus on Pan-Cancer Analysis examines the similarities and differences among the genomic and cellular alterations found in the first dozen tumor types to be profiled by The Cancer Genome Atlas (TCGA) Research Network. This first look across cancers offers new tools in genomics and bioinformatics and the prospect of repurposing targeted therapies to be directed by the molecular pathology of tumors in addition to their clinical classification. News and Views Top Germline PAX5 mutations and B cell leukemia   pp1104 - 1105 R Katherine Hyde and P Paul Liu doi:10.1038/ng.2778 The transcription factor PAX5 is required for normal B cell development and is frequently mutated or deleted in B cell precursor acute lymphoblastic leukemia (B-ALL). A new study demonstrates that germline hypomorphic mutations of PAX5 are associated with susceptibility to B-ALL, implicating PAX5 in a growing list of hematopoietic transcription factors mutated in familial leukemia predisposition syndromes. See also: Letter by Shah et al. Genomics informs glioblastoma biology   pp1105 - 1107 David L Schonberg, Shideng Bao and Jeremy N Rich doi:10.1038/ng.2775 Identifying genomic alterations in cancer does not guarantee therapeutic benefit. A new study combining DNA and RNA sequencing with functional validation uncovers new genetic driver alterations in glioblastoma with potential for clinical translation. See also: Article by Frattini et al. Complex genetics of drug resistance in Mycobacterium tuberculosis   pp1107 - 1108 Digby F Warner and Valerie Mizrahi doi:10.1038/ng.2769 Three new studies have used whole-genome sequencing of M. tuberculosis to demonstrate unexpected complexity in the modern evolution of drug-resistant tuberculosis, and a fourth study suggests a close evolutionary relationship between the pathogen and its human host over a period of 70,000 years. Collectively, the observations in these studies suggest that future strategies to tackle drug-resistant tuberculosis must integrate host genetics with detailed strain epidemiology. See also: Article by Comas et al. | Article by Farhat et al. | Article by Safi et al. | Letter by Zhang et al. Genetics JOBS of the week Faculty Positions in Cancer Biology / Genetics OMRF Postdoctoral Associate in the Genetics of Reading Disability (Dyslexia) Yale University School of Medicine Post-doctoral / PhD student positions in plant genetics University of Tübingen Faculty Position - Molecular Biology & Genetics Massachuesetts General Hospital / Harvard Medical School Molecular genetics of wheat flowering University of California, Davis More Science jobs from Genetics EVENT 13th Congress of Medical Biology and Genetics 27.-30.10.13 Aydin, Turkey More science events from Research Highlights Top Resistance in multiple myeloma | Embryonic epigenetic chimerism | Hedgehog agonist for Down syndrome | Epileptic encephalopathy genes | Neocortex enhancers Commentaries Top The Cancer Genome Atlas Pan-Cancer analysis project OPEN   pp1113 - 1120 The Cancer Genome Atlas Research Network, John N Weinstein, Eric A Collisson, Gordon B Mills, Kenna R Mills Shaw, Brad A Ozenberger, Kyle Ellrott, Ilya Shmulevich, Chris Sander & Joshua M Stuart doi:10.1038/ng.2764 Current clinical practice is organized according to tissue or organ of origin of tumors. Now, The Cancer Genome Atlas (TCGA) Research Network has started to identify genomic and other molecular commonalities among a dozen different types of cancer. Emerging similarities and contrasts will form the basis for targeted therapies of the future and for repurposing existing therapies by molecular rather than histological similarities of the diseases. Enabling transparent and collaborative computational analysis of 12 tumor types within The Cancer Genome Atlas OPEN   pp1121 - 1126 Larsson Omberg, Kyle Ellrott, Yuan Yuan, Cyriac Kandoth, Chris Wong, Michael R Kellen, Stephen H Friend, Josh Stuart, Han Liang & Adam A Margolin doi:10.1038/ng.2761 Larsson Omberg and colleagues write a Commentary describing the collaborative model used by the Pan-Cancer Working Group of The Cancer Genome Atlas. Pan-Cancer members used the Synapse software platform to share and evolve data, results and methods to perform integrative analyses of genome-wide molecular data for 12 cancer types. Analysis Top Emerging landscape of oncogenic signatures across human cancers OPEN   pp1127 - 1133 Giovanni Ciriello, Martin L Miller, Bülent Arman Aksoy, Yasin Senbabaoglu, Nikolaus Schultz & Chris Sander doi:10.1038/ng.2762 Chris Sander and colleagues have extracted significant functional events from 12 tumor types. Tumors can be classified as being driven largely by either mutation or copy number changes, and, within this division, subclasses of cross-tissue patterns of events are discerned that suggest sets of combinatorial therapies. Pan-cancer patterns of somatic copy number alteration OPEN   pp1134 - 1140 Travis I Zack, Steven E Schumacher, Scott L Carter, Andrew D Cherniack, Gordon Saksena, Barbara Tabak, Michael S Lawrence, Cheng-Zhong Zhang, Jeremiah Wala, Craig H Mermel, Carrie Sougnez, Stacey B Gabriel, Bryan Hernandez, Hui Shen, Peter W Laird, Gad Getz, Matthew Meyerson & Rameen Beroukhim doi:10.1038/ng.2760 Rameen Beroukhim and colleagues analyzed somatic structural alterations in 12 tumor types. Whole-genome doubling was found in over a third of all cancers, associated with TP53 mutation. Fifteen new significantly mutated candidate driver genes were found associated with recurrently amplified or deleted regions. Advertisement The 8th International Conference on Genomics  ICG-8, co-organized by BGI and GigaScience from Oct. 30 to Nov. 1, 2013 in Shenzhen, China, will consist of 18 sessions featuring over 80 presentations. It will focus on the latest developments in human diseases, bioinfomatics, plant and animal genomics and metagenomics. Register by September 30 to save up to $180!   Articles Top The integrated landscape of driver genomic alterations in glioblastoma   pp1141 - 1149 Veronique Frattini, Vladimir Trifonov, Joseph Minhow Chan, Angelica Castano, Marie Lia, Francesco Abate, Stephen T Keir, Alan X Ji, Pietro Zoppoli, Francesco Niola, Carla Danussi, Igor Dolgalev, Paola Porrati, Serena Pellegatta, Adriana Heguy, Gaurav Gupta, David J Pisapia, Peter Canoll, Jeffrey N Bruce, Roger E McLendon, Hai Yan, Ken Aldape, Gaetano Finocchiaro, Tom Mikkelsen, Gilbert G Privé, Darell D Bigner, Anna Lasorella, Raul Rabadan & Antonio Iavarone doi:10.1038/ng.2734 Anna Lasorella, Raul Rabadan, Antonio Iavarone and colleagues report an integrated analysis of genomic alterations in glioblastoma. They identify and functionally validate several new driver events, including loss-of-function mutations in CTNND2 and recurrent EGFR fusions. See also: News and Views by Schonberg et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia   pp1150 - 1159 Stephan Ripke, Colm O'Dushlaine, Kimberly Chambert, Jennifer L Moran, Anna K Kähler, Susanne Akterin, Sarah E Bergen, Ann L Collins, James J Crowley, Menachem Fromer, Yunjung Kim, Sang Hong Lee, Patrik K E Magnusson, Nick Sanchez, Eli A Stahl, Stephanie Williams, Naomi R Wray, Kai Xia, Francesco Bettella, Anders D Borglum, Brendan K Bulik-Sullivan, Paul Cormican, Nick Craddock, Christiaan de Leeuw, Naser Durmishi, Michael Gill, Vera Golimbet, Marian L Hamshere, Peter Holmans, David M Hougaard, Kenneth S Kendler, Kuang Lin, Derek W Morris, Ole Mors, Preben B Mortensen, Benjamin M Neale, Francis A O'Neill, Michael J Owen, Milica Pejovic Milovancevic, Danielle Posthuma, John Powell, Alexander L Richards, Brien P Riley, Douglas Ruderfer, Dan Rujescu, Engilbert Sigurdsson, Teimuraz Silagadze, August B Smit, Hreinn Stefansson, Stacy Steinberg, Jaana Suvisaari, Sarah Tosato, Matthijs Verhage, James T Walters, Multicenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, Elvira Bramon, Aiden P Corvin, Michael C O'Donovan, Kari Stefansson, Edward Scolnick, Shaun Purcell, Steven A McCarroll, Pamela Sklar, Christina M Hultman & Patrick F Sullivan doi:10.1038/ng.2742 Patrick Sullivan and colleagues report a multi-stage genome-wide association study for schizophrenia in a Swedish population. They identify 13 loci newly associated with schizophrenia. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene   pp1160 - 1167 Patrick R Sosnay, Karen R Siklosi, Fredrick Van Goor, Kyle Kaniecki, Haihui Yu, Neeraj Sharma, Anabela S Ramalho, Margarida D Amaral, Ruslan Dorfman, Julian Zielenski, David L Masica, Rachel Karchin, Linda Millen, Philip J Thomas, George P Patrinos, Mary Corey, Michelle H Lewis, Johanna M Rommens, Carlo Castellani, Christopher M Penland & Garry R Cutting doi:10.1038/ng.2745 Garry Cutting and colleagues report a comprehensive functional and clinical analysis of CFTR variants reported in cystic fibrosis. They determine that 128 of 160 CFTR variants with an allele frequency of >0.01% are causal for disease. The genome of the hydatid tapeworm Echinococcus granulosus OPEN   pp1168 - 1175 Huajun Zheng, Wenbao Zhang, Liang Zhang, Zhuangzhi Zhang, Jun Li, Gang Lu, Yongqiang Zhu, Yuezhu Wang, Yin Huang, Jing Liu, Hui Kang, Jie Chen, Lijun Wang, Aojun Chen, Shuting Yu, Zhengchao Gao, Lei Jin, Wenyi Gu, Zhiqin Wang, Li Zhao, Baoxin Shi, Hao Wen, Renyong Lin, Malcolm K Jones, Brona Brejova, Tomas Vinar, Guoping Zhao, Donald P McManus, Zhu Chen, Yan Zhou & Shengyue Wang doi:10.1038/ng.2757 Shengyue Wang and colleagues report the draft genome sequence and transcriptome analysis for Echinococcus granulosus, a parasitic helminth and cause of human hydatid disease. Their comparative genomic analysis identifies genes acquired by E. granulosus that are associated with host immune response, parasite survival and growth. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans   pp1176 - 1182 Iñaki Comas, Mireia Coscolla, Tao Luo, Sonia Borrell, Kathryn E Holt, Midori Kato-Maeda, Julian Parkhill, Bijaya Malla, Stefan Berg, Guy Thwaites, Dorothy Yeboah-Manu, Graham Bothamley, Jian Mei, Lanhai Wei, Stephen Bentley, Simon R Harris, Stefan Niemann, Roland Diel, Abraham Aseffa, Qian Gao, Douglas Young & Sebastien Gagneux doi:10.1038/ng.2744 Iñaki Comas and colleagues report whole-genome sequencing and analysis of 259 Mycobacterium tuberculosis complex strains, providing a survey of global diversity and facilitating evolutionary analyses. Their phylogeographic analysis suggests the emergence of M. tuberculosis complex strains about 70,000 years ago in Africa, with expansion correlated with increased human population density during the Neolithic Demographic Transition. See also: News and Views by Warner & Mizrahi Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis   pp1183 - 1189 Maha R Farhat, B Jesse Shapiro, Karen J Kieser, Razvan Sultana, Karen R Jacobson, Thomas C Victor, Robin M Warren, Elizabeth M Streicher, Alistair Calver, Alex Sloutsky, Devinder Kaur, Jamie E Posey, Bonnie Plikaytis, Marco R Oggioni, Jennifer L Gardy, James C Johnston, Mabel Rodrigues, Patrick K C Tang, Midori Kato-Maeda, Mark L Borowsky, Bhavana Muddukrishna, Barry N Kreiswirth, Natalia Kurepina, James Galagan, Sebastien Gagneux, Bruce Birren, Eric J Rubin, Eric S Lander, Pardis C Sabeti & Megan Murray doi:10.1038/ng.2747 Maha Farhat, Megan Murray and colleagues report whole-genome sequencing of 116 Mycobacterium tuberculosis strains selected to be representative of both global diversity and drug resistance. The authors develop a new method to search for resistance markers in microbial genomes based on reconstructing a genome-wide phylogeny and identifying regions showing convergent evolution, and they use this method to identify 39 new candidate drug resistance regions in the M. tuberculosis genome. See also: News and Views by Warner & Mizrahi Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-D-arabinose biosynthetic and utilization pathway genes   pp1190 - 1197 Hassan Safi, Subramanya Lingaraju, Anita Amin, Soyeon Kim, Marcus Jones, Michael Holmes, Michael McNeil, Scott N Peterson, Delphi Chatterjee, Robert Fleischmann & David Alland doi:10.1038/ng.2743 David Alland and colleagues report sequencing of Mycobacterium tuberculosis strains under ethambutol drug selection. They follow the multistep progression in acquisition of ethambutol resistance in clinical isolates, finding that an interaction of mutations in several genes in DPA biosynthetic and utilization pathways influence the level of resistance as measured by the minimal inhibitory concentration. See also: News and Views by Warner & Mizrahi Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues   pp1198 - 1206 Gary C Hon, Nisha Rajagopal, Yin Shen, David F McCleary, Feng Yue, My D Dang & Bing Ren doi:10.1038/ng.2746 Bing Ren and colleagues generate base-resolution maps of DNA methylation in 17 adult mouse tissues. They identify tissue-specific differentially methylated regions and show that they occur at distal cis-regulatory elements, many of which bear enhancer features. Mapping the fine structure of a eukaryotic promoter input-output function   pp1207 - 1215 Arun S Rajkumar, Nicolas Dénervaud & Sebastian J Maerkl doi:10.1038/ng.2729 Sebastian Maerkl and colleagues use single-cell measurements to show that the output of the yeast PHO5 promoter can be precisely tuned by subtle changes in binding-site affinity for the Pho4 transcription factor. These results provide insights into how transcription-factor binding sites regulate gene expression and demonstrate the feasibility of developing quantitative models of transcriptional regulatory networks. Letters Top Variants in CPA1 are strongly associated with early onset chronic pancreatitis   pp1216 - 1220 Heiko Witt, Sebastian Beer, Jonas Rosendahl, Jian-Min Chen, Giriraj Ratan Chandak, Atsushi Masamune, Melinda Bence, Richárd Szmola, Grzegorz Oracz, Milan Macek Jr, Eesh Bhatia, Sandra Steigenberger, Denise Lasher, Florence Bühler, Catherine Delaporte, Johanna Tebbing, Maren Ludwig, Claudia Pilsak, Karolin Saum, Peter Bugert, Emmanuelle Masson, Sumit Paliwal, Seema Bhaskar, Agnieszka Sobczynska-Tomaszewska, Daniel Bak, Ivan Balascak, Gourdas Choudhuri, D Nageshwar Reddy, G Venkat Rao, Varghese Thomas, Kiyoshi Kume, Eriko Nakano, Yoichi Kakuta, Tooru Shimosegawa, Lukasz Durko, András Szabó, Andrea Schnúr, Péter Hegyi, Zoltán Rakonczay Jr, Roland Pfützer, Alexander Schneider, David Alexander Groneberg, Markus Braun, Hartmut Schmidt, Ulrike Witt, Helmut Friess, Hana Algül, Olfert Landt, Markus Schuelke, Renate Krüger, Bertram Wiedenmann, Frank Schmidt, Klaus-Peter Zimmer, Peter Kovacs, Michael Stumvoll, Matthias Blüher, Thomas Müller, Andreas Janecke, Niels Teich, Robert Grützmann, Hans-Ulrich Schulz, Joachim Mössner, Volker Keim, Matthias Löhr, Claude Férec & Miklós Sahin-Tóth doi:10.1038/ng.2730 Heiko Witt, Miklós Sahin-Tóth and colleagues show that loss-of-function variants in CPA1 are strongly associated with early onset chronic pancreatitis. On the basis of their findings, they propose that the mechanism may involve misfolding-induced endoplasmic reticulum stress rather than elevated trypsin activity. Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk   pp1221 - 1225 Daniel Chubb, Niels Weinhold, Peter Broderick, Bowang Chen, David C Johnson, Asta Försti, Jayaram Vijayakrishnan, Gabriele Migliorini, Sara E Dobbins, Amy Holroyd, Dirk Hose, Brian A Walker, Faith E Davies, Walter A Gregory, Graham H Jackson, Julie A Irving, Guy Pratt, Chris Fegan, James A L Fenton, Kai Neben, Per Hoffmann, Markus M Nöthen, Thomas W Mühleisen, Lewin Eisele, Fiona M Ross, Christian Straka, Hermann Einsele, Christian Langer, Elisabeth Dörner, James M Allan, Anna Jauch, Gareth J Morgan, Kari Hemminki, Richard S Houlston & Hartmut Goldschmidt doi:10.1038/ng.2733 Richard Houlston and colleagues report a genome-wide association study of multiple myeloma and identify four loci associated with susceptibility to this malignancy. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia   pp1226 - 1231 Sohela Shah, Kasmintan A Schrader, Esmé Waanders, Andrew E Timms, Joseph Vijai, Cornelius Miething, Jeremy Wechsler, Jun Yang, James Hayes, Robert J Klein, Jinghui Zhang, Lei Wei, Gang Wu, Michael Rusch, Panduka Nagahawatte, Jing Ma, Shann-Ching Chen, Guangchun Song, Jinjun Cheng, Paul Meyers, Deepa Bhojwani, Suresh Jhanwar, Peter Maslak, Martin Fleisher, Jason Littman, Lily Offit, Rohini Rau-Murthy, Megan Harlan Fleischut, Marina Corines, Rajmohan Murali, Xiaoni Gao, Christopher Manschreck, Thomas Kitzing, Vundavalli V Murty, Susana C Raimondi, Roland P Kuiper, Annet Simons, Joshua D Schiffman, Kenan Onel, Sharon E Plon, David A Wheeler, Deborah Ritter, David S Ziegler, Kathy Tucker, Rosemary Sutton, Georgia Chenevix-Trench, Jun Li, David G Huntsman, Samantha Hansford, Janine Senz, Tom Walsh, Ming Lee, Christopher N Hahn, Kathryn G Roberts, Mary-Claire King, Sarah M Lo, Ross L Levine, Agnes Viale, Nicholas D Socci, Katherine L Nathanson, Hamish S Scott, Mark Daly, Steven M Lipkin, Scott W Lowe, James R Downing, David Altshuler, John T Sandlund, Marshall S Horwitz, Charles G Mullighan & Kenneth Offit doi:10.1038/ng.2754 Marshall Horwitz, Charles Mullighan, Kenneth Offit and colleagues report the identification of a recurrent germline PAX5 mutation in families with pre-B cell acute lymphoblastic leukemia. They also identify sporadic cases of this leukemia with the same mutation that arose somatically. See also: News and Views by Hyde & Liu Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms   pp1232 - 1237 Ayana Kon, Lee-Yung Shih, Masashi Minamino, Masashi Sanada, Yuichi Shiraishi, Yasunobu Nagata, Kenichi Yoshida, Yusuke Okuno, Masashige Bando, Ryuichiro Nakato, Shumpei Ishikawa, Aiko Sato-Otsubo, Genta Nagae, Aiko Nishimoto, Claudia Haferlach, Daniel Nowak, Yusuke Sato, Tamara Alpermann, Masao Nagasaki, Teppei Shimamura, Hiroko Tanaka, Kenichi Chiba, Ryo Yamamoto, Tomoyuki Yamaguchi, Makoto Otsu, Naoshi Obara, Mamiko Sakata-Yanagimoto, Tsuyoshi Nakamaki, Ken Ishiyama, Florian Nolte, Wolf-Karsten Hofmann, Shuichi Miyawaki, Shigeru Chiba, Hiraku Mori, Hiromitsu Nakauchi, H Phillip Koeffler, Hiroyuki Aburatani, Torsten Haferlach, Katsuhiko Shirahige, Satoru Miyano & Seishi Ogawa doi:10.1038/ng.2731 The cohesin complex mediates sister chromatid cohesion during cell division. Now, Seishi Ogawa and colleagues report largely mutually exclusive mutations in multiple members of the cohesin complex in acute myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, chronic myelogenous leukemia and classical myeloproliferative neoplasms. Systematic identification of trans eQTLs as putative drivers of known disease associations   pp1238 - 1243 Harm-Jan Westra, Marjolein J Peters, Tõnu Esko, Hanieh Yaghootkar, Claudia Schurmann, Johannes Kettunen, Mark W Christiansen, Benjamin P Fairfax, Katharina Schramm, Joseph E Powell, Alexandra Zhernakova, Daria V Zhernakova, Jan H Veldink, Leonard H Van den Berg, Juha Karjalainen, Sebo Withoff, André G Uitterlinden, Albert Hofman, Fernando Rivadeneira, Peter A C 't Hoen, Eva Reinmaa, Krista Fischer, Mari Nelis, Lili Milani, David Melzer, Luigi Ferrucci, Andrew B Singleton, Dena G Hernandez, Michael A Nalls, Georg Homuth, Matthias Nauck, Dörte Radke, Uwe Völker, Markus Perola, Veikko Salomaa, Jennifer Brody, Astrid Suchy-Dicey, Sina A Gharib, Daniel A Enquobahrie, Thomas Lumley, Grant W Montgomery, Seiko Makino, Holger Prokisch, Christian Herder, Michael Roden, Harald Grallert, Thomas Meitinger, Konstantin Strauch, Yang Li, Ritsert C Jansen, Peter M Visscher, Julian C Knight, Bruce M Psaty, Samuli Ripatti, Alexander Teumer, Timothy M Frayling, Andres Metspalu, Joyce B J van Meurs & Lude Franke doi:10.1038/ng.2756 Lude Franke and colleagues report the results of a large expression QTL study performed on peripheral blood samples from 5,311 individuals. They identify trans-eQTL effects for 103 independent loci that were previously associated with complex traits at genome-wide significance, suggesting that this approach can provide insights into the downstream effects of many trait-associated variants. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting   pp1244 - 1248 Liat Samuelov, Ofer Sarig, Robert M Harmon, Debora Rapaport, Akemi Ishida-Yamamoto, Ofer Isakov, Jennifer L Koetsier, Andrea Gat, Ilan Goldberg, Reuven Bergman, Ronen Spiegel, Ori Eytan, Shamir Geller, Sarit Peleg, Noam Shomron, Christabelle S M Goh, Neil J Wilson, Frances J D Smith, Elizabeth Pohler, Michael A Simpson, W H Irwin McLean, Alan D Irvine, Mia Horowitz, John A McGrath, Kathleen J Green & Eli Sprecher doi:10.1038/ng.2739 Eli Sprecher, Kathleen Green and colleagues show that biallelic mutations in DSG1 cause a syndrome featuring severe dermatitis, multiple allergies and metabolic wasting. The mutations abolish expression of desmoglein 1, resulting in loss of cell adhesion accompanied by increased expression of several allergy-related cytokines. Glutathione peroxidase activity is neuroprotective in models of Huntington's disease   pp1249 - 1254 Robert P Mason, Massimiliano Casu, Nicola Butler, Carlo Breda, Susanna Campesan, Jannine Clapp, Edward W Green, Devyani Dhulkhed, Charalambos P Kyriacou & Flaviano Giorgini doi:10.1038/ng.2732 Flaviano Giorgini and colleagues perform an overexpression screen in yeast to identify genes that can suppress the toxic effects of the mutant Huntington's disease protein Htt. They identify glutathione peroxidase activity as a robust suppressor of mutant Htt toxicity and validate these protective effects in Drosophila and in mammalian cell models. Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance   pp1255 - 1260 Hongtai Zhang, Dongfang Li, Lili Zhao, Joy Fleming, Nan Lin, Ting Wang, Zhangyi Liu, Chuanyou Li, Nicholas Galwey, Jiaoyu Deng, Ying Zhou, Yuanfang Zhu, Yunrong Gao, Tong Wang, Shihua Wang, Yufen Huang, Ming Wang, Qiu Zhong, Lin Zhou, Tao Chen, Jie Zhou, Ruifu Yang, Guofeng Zhu, Haiying Hang, Jia Zhang, Fabin Li, Kanglin Wan, Jun Wang, Xian-En Zhang & Lijun Bi doi:10.1038/ng.2735 Lijun Bi and colleagues report sequencing of 161 tuberculosis strains from China, including 44 drug-sensitive, 94 MDR and 23 XDR isolates. They identify 72 new genes and 28 new intergenic regions significantly associated with drug resistance. See also: News and Views by Warner & Mizrahi Corrigenda Top Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis   p1261 Vikram P Sharma, Aimée L Fenwick, Mia S Brockop, Simon J McGowan, Jacqueline A C Goos, A Jeannette M Hoogeboom, Angela F Brady, Nu Owase Jeelani, Sally Ann Lynch, John B Mulliken, Dylan J Murray, Julie M Phipps, Elizabeth Sweeney, Susan E Tomkins, Louise C Wilson, Sophia Bennett, Richard J Cornall, John Broxholme, Alexander Kanapin, 500 Whole-Genome Sequences (WGS500) Consortium, David Johnson, Steven A Wall, Peter J van der Spek, Irene M J Mathijssen, Robert E Maxson, Stephen R F Twigg & Andrew O M Wilkie doi:10.1038/ng1013-1261a The burden of faulty proofreading in colon cancer   p1261 Somasekar Seshagiri doi:10.1038/ng1013-1261b Top Advertisement Frontiers in Genetics innovative peer review process guarantees the most accurate, efficient and impartial reviews in academic publishing, with genuinely collaborative interactions between authors and referees. 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